Department of Anesthesiology, the First Affiliated Hospital, Wenzhou Medical University, Zhejiang, China.
Reg Anesth Pain Med. 2018 Nov;43(8):838-843. doi: 10.1097/AAP.0000000000000834.
Although intravenous lipid emulsion has been proved a powerful antidote for local anesthetic toxicity, there are few pharmacokinetic data on using lipid infusion as a pretreatment for other clinical applications. We assessed the influence of lipid pretreatment on the pharmacodynamics and pharmacokinetics of levobupivacaine.
Altogether, 12 patients undergoing below-knee surgery for a fracture were randomly assigned to 2 groups (6 patients per group): pretreatment with 1.5 mL/kg lipid infusion (lipid group) or saline infusion (control subjects) followed by complete femoral and sciatic nerve block with 0.375% levobupivacaine (2.5 mg/kg). Total and free (non-protein bound) plasma levobupivacaine concentrations and triglycerides in the lipid group were determined.
Results were given as means ± SD. Total and free maximum plasma levobupivacaine concentrations were lower in the lipid group than in control subjects (865 ± 98 vs 1145 ± 177 μg/L and 56.8 ± 7.5 vs 78.2 ± 13.7 μg/L, respectively; P < 0.01). Apparent volume of distribution and clearance were higher in the lipid group than in control subjects (211 ± 35 vs 170 ± 21 L and 35.1 ± 8.0 vs 25.8 ± 2.6 L/h, respectively; P < 0.05). Triglyceride level was significantly higher at the end of lipid infusion than baseline values (7.59 ± 1.32 vs 1.34 ± 0.39 mmol/L; P < 0.01).
Lipid pretreatment increased the apparent volume of distribution and clearance and decreased the maximum total and free levobupivacaine concentrations, thus offering a reasonable explanation for the effects of lipids on local anesthesia-related toxicity in humans. Rapid lipid infusion induced hypertriglyceridemia without other apparent risks in this study.
This study was registered at the Chinese Clinical Trial Registry, identifier ChiCTR-TRC-14005203.
虽然静脉内脂肪乳剂已被证实是一种强力的局部麻醉毒性解毒剂，但关于脂肪输注作为其他临床应用的预处理的药代动力学数据很少。我们评估了脂肪预处理对左旋布比卡因药效学和药代动力学的影响。
总共 12 例因骨折行膝下手术的患者被随机分为 2 组（每组 6 例）：脂肪输注（脂质组）或生理盐水输注（对照组）预处理，然后用 0.375%左旋布比卡因（2.5 mg/kg）行股神经和坐骨神经完全阻滞。测定脂质组的总血浆和游离（非蛋白结合）左旋布比卡因浓度和甘油三酯浓度。
结果表示为均数±标准差。脂质组的总血浆和游离最大左旋布比卡因浓度均低于对照组（865±98 比 1145±177μg/L 和 56.8±7.5 比 78.2±13.7μg/L；P＜0.01）。脂质组的表观分布容积和清除率均高于对照组（211±35 比 170±21 L 和 35.1±8.0 比 25.8±2.6 L/h；P＜0.05）。脂质输注结束时的甘油三酯水平明显高于基线值（7.59±1.32 比 1.34±0.39 mmol/L；P＜0.01）。
脂肪预处理增加了表观分布容积和清除率，降低了最大总血浆和游离左旋布比卡因浓度，因此为脂肪对人类局部麻醉相关毒性的影响提供了合理的解释。在本研究中，快速输注脂肪引起了高甘油三酯血症，但没有其他明显的风险。
本研究在中国临床试验注册中心注册，注册号 ChiCTR-TRC-14005203。
